Background: Despite evidence suggesting that early metabolic dysfunction impacts cardiovascular disease risk, current guidelines focus on risk assessments later in life, missing early transitions in metabolic risk that may represent opportunities for averting the development of cardiovascular disease.

Methods and results: In 4420 young adults in the Coronary Artery Risk Development in Young Adults (CARDIA) study, we defined a &ldquo;metabolic&rdquo; risk score based on components of the Third Report of the Adult Treatment Panel's definition of metabolic syndrome. Using latent class trajectory analysis adjusted for sex, race, and time&#8208;dependent body mass index, we identified 6 distinct metabolic trajectories over time, specified by initial and final risk: low&#8208;stable, low&#8208;worsening, high&#8208;stable, intermediate&#8208;worsening, intermediate&#8208;stable, and high&#8208;worsening. Overall, individuals gained weight over time in CARDIA with statistically but not clinically different body mass index trend over time. Dysglycemia and dyslipidemia over time were highest in initially high or worsening trajectory groups. Divergence in metabolic trajectories occurred in early adulthood (before age 40), with 2 of 3 individuals experiencing an increase in metabolic risk over time. Membership in a higher&#8208;risk trajectory (defined as initially high or worsening over time) was associated with greater prevalence and extent of coronary artery calcification, left ventricular mass, and decreased left ventricular strain at year 25. Importantly, despite similar rise in body mass index across trajectories over 25&nbsp;years, coronary artery calcification and left ventricular structure and function more closely tracked risk factor trajectories.

Conclusions: Transitions in metabolic risk occur early in life. Obesity&#8208;related metabolic dysfunction is related to subclinical cardiovascular phenotypes independent of evolution in body mass index, including coronary artery calcification and myocardial hypertrophy and dysfunction.

jah31816-fig-0002: Trends in body mass index (BMI) (A), waist circumference (WC) (B), and ratio of WC/BMI (C) over time in the Coronary Artery Risk Development in Young Adults (CARDIA) trial, stratified by trajectory group computed using linear mixed‐effects models with discrete time points for each CARDIA exam and exam×trajectory group interaction terms. Over time, all groups had similar increases in BMI and WC. While worsening groups had stable WC/BMI ratios (P≥0.29 for exam 1 vs exam 8), the stable groups all had declining WC/BMI ratios (P≤0.0005 for exam 1 vs exam 8), suggesting greater proportionate increases in abdominal adiposity in the metabolically worsening groups.

Mentions:
On average, participants who attended the final year 25 CARDIA examination were heavier than those attending the initial study visit (initial BMI 24.4±4.9 kg/m2 to final BMI 30.1±7.2 kg/m2), with greater central obesity (by waist circumference), dysglycemia, and a more proatherogenic lipid profile. Of 4420 participants at baseline, 1516 (34%) were overweight or obese (by BMI ≥25 kg/m2). Of the 3274 CARDIA participants in our analytic sample at year 25, 2435 (74%) were overweight or obese. While individuals on average gained weight over time (with statistically significant differences in weight gain across trajectories, P<0.0001), among those participants with BMI assessed at year 0 and year 25 in our analytic cohort, there was an increase in BMI and central obesity, with a similar pattern across all trajectories (Figure 2A and 2B). In addition, we considered waist circumference to BMI ratio (a marker of preferential visceral fat stores; Figure 2C). We found that individuals with worsening metabolic trajectories have a stable ratio over time, while individuals with stable trajectories have a declining ratio, suggesting that less excess weight gained over time is visceral in these individuals. Of note, waist circumference also appeared to have a similar association with baseline metabolic score in lean and overweight/obese individuals (Figure S1).

jah31816-fig-0002: Trends in body mass index (BMI) (A), waist circumference (WC) (B), and ratio of WC/BMI (C) over time in the Coronary Artery Risk Development in Young Adults (CARDIA) trial, stratified by trajectory group computed using linear mixed‐effects models with discrete time points for each CARDIA exam and exam×trajectory group interaction terms. Over time, all groups had similar increases in BMI and WC. While worsening groups had stable WC/BMI ratios (P≥0.29 for exam 1 vs exam 8), the stable groups all had declining WC/BMI ratios (P≤0.0005 for exam 1 vs exam 8), suggesting greater proportionate increases in abdominal adiposity in the metabolically worsening groups.

Mentions:
On average, participants who attended the final year 25 CARDIA examination were heavier than those attending the initial study visit (initial BMI 24.4±4.9 kg/m2 to final BMI 30.1±7.2 kg/m2), with greater central obesity (by waist circumference), dysglycemia, and a more proatherogenic lipid profile. Of 4420 participants at baseline, 1516 (34%) were overweight or obese (by BMI ≥25 kg/m2). Of the 3274 CARDIA participants in our analytic sample at year 25, 2435 (74%) were overweight or obese. While individuals on average gained weight over time (with statistically significant differences in weight gain across trajectories, P<0.0001), among those participants with BMI assessed at year 0 and year 25 in our analytic cohort, there was an increase in BMI and central obesity, with a similar pattern across all trajectories (Figure 2A and 2B). In addition, we considered waist circumference to BMI ratio (a marker of preferential visceral fat stores; Figure 2C). We found that individuals with worsening metabolic trajectories have a stable ratio over time, while individuals with stable trajectories have a declining ratio, suggesting that less excess weight gained over time is visceral in these individuals. Of note, waist circumference also appeared to have a similar association with baseline metabolic score in lean and overweight/obese individuals (Figure S1).

Background: Despite evidence suggesting that early metabolic dysfunction impacts cardiovascular disease risk, current guidelines focus on risk assessments later in life, missing early transitions in metabolic risk that may represent opportunities for averting the development of cardiovascular disease.

Methods and results: In 4420 young adults in the Coronary Artery Risk Development in Young Adults (CARDIA) study, we defined a &ldquo;metabolic&rdquo; risk score based on components of the Third Report of the Adult Treatment Panel's definition of metabolic syndrome. Using latent class trajectory analysis adjusted for sex, race, and time&#8208;dependent body mass index, we identified 6 distinct metabolic trajectories over time, specified by initial and final risk: low&#8208;stable, low&#8208;worsening, high&#8208;stable, intermediate&#8208;worsening, intermediate&#8208;stable, and high&#8208;worsening. Overall, individuals gained weight over time in CARDIA with statistically but not clinically different body mass index trend over time. Dysglycemia and dyslipidemia over time were highest in initially high or worsening trajectory groups. Divergence in metabolic trajectories occurred in early adulthood (before age 40), with 2 of 3 individuals experiencing an increase in metabolic risk over time. Membership in a higher&#8208;risk trajectory (defined as initially high or worsening over time) was associated with greater prevalence and extent of coronary artery calcification, left ventricular mass, and decreased left ventricular strain at year 25. Importantly, despite similar rise in body mass index across trajectories over 25&nbsp;years, coronary artery calcification and left ventricular structure and function more closely tracked risk factor trajectories.

Conclusions: Transitions in metabolic risk occur early in life. Obesity&#8208;related metabolic dysfunction is related to subclinical cardiovascular phenotypes independent of evolution in body mass index, including coronary artery calcification and myocardial hypertrophy and dysfunction.